Cross-linked polyallylamine polymers have found many therapeutic applications. See for example, WO 98/57652, JP 07309766-A and U.S. Pat. Nos. 5,618,530, 5,679,717, 5,693,675 and 5,607,669 for reducing blood cholesterol levels by reducing reabsorption of bile acids, U.S. Pat. No. 5,702,696 for decreasing the absorption of dietary iron from the gastrointestinal track, and WO 96/21454 and U.S. Pat. No. 5,496,545 for removing phosphate from the gastrointestinal track. Further, JP 05244915 discloses the use of cross-linked polyamine polymers as a food preservative.
Methods to produce cross-linked polyamine polymers are known. See for example, the references cited hereinabove and U.S. Pat. No. 4,605,701, DE 4227019 A1 and EP 732352 A1. These references disclose cross-linking the polyallylamine polymer by reacting the polymer with a suitable cross-linking agent in aqueous caustic solution or an aqueous caustic solution and immiscible solvent mixture.
The existing methods to produce cross-linked polyamine polymers create difficult and costly handling and cleanup procedures, especially in an industrial production process. For example in U.S. Pat. Nos. 5,618,530, 5,679,717, 5,693,675, 5,702,696 and 5,607,669 the cross-linked polyallylamine forms a continuous mass within the reaction vessel after it congeals which is impractical on a large scale. Further, when the cross-linking reaction occurs in a basic aqueous solution the removal of undesirable impurities, such as salts, e.g., sodium chloride, as well as unreacted allylamine monomer, low molecular weight polyallylamine polymer, low molecular weight compounds from initiator degradation during and after the free-radical polymerization of the allylamine monomer, solvents, etc., is very complicated as it must be performed on the solid, insoluble, cross-linked polyallylamine polymer. Moreover, when using a basic aqueous solution and dispersion solvent mixture, such as disclosed in WO 98/57652, the solvent, e.g., acetonitrile, must be reclaimed or disposed of. The present invention addresses these problems and gives a more practical solution to them.